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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mes</journal-id><journal-title-group><journal-title xml:lang="ru">Экстремальная биомедицина</journal-title><trans-title-group xml:lang="en"><trans-title>Extreme Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">3033-8964</issn><issn pub-type="epub">3033-8972</issn><publisher><publisher-name>Centre for Strategic Planning of the Federal Medical and Biological Agency</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.47183/mes.2022.047</article-id><article-id custom-type="elpub" pub-id-type="custom">mes-207</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL RESEARCH</subject></subj-group></article-categories><title-group><article-title>Оценка методов инактивирования вируса лейкоза птиц при производстве гриппозных вакцин</article-title><trans-title-group xml:lang="en"><trans-title>Evaluation of methods of avian leucosis virus inactivation in production of influenza vaccines</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Савина</surname><given-names>Н. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Savina</surname><given-names>N. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>St. Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Екимов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ekimov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Алексей Александрович Екимов</p><p>ул. Свободы, д. 52, Красное Село, г. Санкт-Петербург, 198320</p></bio><bio xml:lang="en"><p>Alexey Alexandrovich Ekimov</p><p>Svobody, 52, Krasnoe Selo, St. Petersburg, 198320</p></bio><email xlink:type="simple">a.a.ekimov@niivs.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шуклина</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shuklina</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>St. Petersburg</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Трухин</surname><given-names>В. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Trukhin</surname><given-names>V. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>St. Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Евтушенко</surname><given-names>А. Э.</given-names></name><name name-style="western" xml:lang="en"><surname>Evtushenko</surname><given-names>A. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>St. Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Жиренкина</surname><given-names>Е. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhirenkina</surname><given-names>E. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>St. Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Степанова</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Stepanova</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>St. Petersburg</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Санкт-Петербургский научно-исследовательский институт вакцин и сывороток и предприятие по производству бактерийных препаратов Федерального медико-биологического агентства</institution><country>Россия</country></aff><aff xml:lang="en"><institution>St. Petersburg Research Institute of Vaccines and Serums and Bacterial Preparations Production Company of the FMBA of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Научно-исследовательский институт гриппа имени А. А. Смородинцева Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Smorodintsev Research Institute of Influenza</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>28</day><month>10</month><year>2024</year></pub-date><volume>24</volume><issue>4</issue><fpage>60</fpage><lpage>65</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Савина Н.Н., Екимов А.А., Шуклина М.А., Трухин В.П., Евтушенко А.Э., Жиренкина Е.Н., Степанова Л.А., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Савина Н.Н., Екимов А.А., Шуклина М.А., Трухин В.П., Евтушенко А.Э., Жиренкина Е.Н., Степанова Л.А.</copyright-holder><copyright-holder xml:lang="en">Savina N.N., Ekimov A.A., Shuklina M.A., Trukhin V.P., Evtushenko A.E., Zhirenkina E.N., Stepanova L.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.extrememedicine.ru/jour/article/view/207">https://www.extrememedicine.ru/jour/article/view/207</self-uri><abstract><p>При производстве инактивированных гриппозных вакцин на стадии инактивации должен быть инактивирован как вирус гриппа, так и возможные вирусные контаминанты, которые могут попасть в вакцину из сырья (куриных эмбрионов). Одним из возможных контаминантов является вирус лейкоза птиц. Инактиваторы должны обеспечивать гарантированное снижение вирусной нагрузки контаминанта не менее чем на 4 lg/мл, что обеспечит его отсутствие в готовой вакцине. Целью работы было осуществить наработку вируса лейкоза для достижения минимального титра 5 lg/мл, оценить снижение титра вируса лейкоза птиц в полупродуктах гриппозных вакцин при воздействии инактиваторов. В исследовании использовали штаммы вируса лейкоза RAV-1 и RAV-2 и полупродукты гриппозных вакцин, такие как вируссодержащая аллантоисная жидкость и вирусные концентраты. Титры вируса лейкоза птиц определяли методом иммуноферментного анализа. Были подобраны условия наработки вируса лейкоза птиц штаммов RAV-1 и RAV-2 в первичной культуре фибробластов эмбрионов кур (ФЭК); рассмотрены основные используемые инактиваторы — β-пропиолактон и УФ-излучение. Выявлено, что спустя 12 ч инактивации β-пропиолактоном вирус лейкоза птиц штамма RAV-1 показал снижение вирусной нагрузки на 4,61 ± 0,46 lg, а вирус лейкоза птиц штамма RAV-2 — на 4,33 ± 0,33 lg, что указывает на эффективное действие β-пропиолактона при инактивации. Проведение инактивации УФ-излучением позволяет снизить вирусную нагрузку штамма RAV-1 на 4,22 ± 0,31 lg, а штамма RAV-2 на 4,44 ± 0,48 lg за 5 мин.</p></abstract><trans-abstract xml:lang="en"><p>The process of production of inactivated influenza vaccines involves a stage of inactivation of both the influenza virus and the possible viral contaminants that can come from the raw materials (chicken embryos). One of such contaminants is the avian leucosis virus. The minimum viral contaminant load reduction that the inactivating agents should guarantee is by 4 lg/ml; this or higher level of the deactivating ability ensures the finished vaccine is free from viral contaminants. The purpose of this work was to cultivate the leucosis virus to the titer of 5 lg/ml (minimum) and to measure the reduction of the avianleucosis virus titer in influenza vaccine intermediates upon exposure to the inactivating agents. The RAV-1 and RAV-2 leucosis virus strains and influenza vaccine intermediates such as virus[<xref ref-type="bibr" rid="cit1">1</xref>]containing allantoic fluid and virus concentrates were used in the study. Avian leucosis virus titers were determined by enzyme immunoassay. We created conditions for cultivation of the RAV-1 and RAV-2 avian leucosis virus strains in the primary culture of chicken embryo fibroblasts (CEF); the inactivating agents considered were the most commonly used β-propiolactone and UV radiation. It was found that after 12 hours of exposure to β-propiolactone, the RAV-1 avian leucosis virus load decreased by 4.61 ± 0.46 lg, and that of RAV-2 strain — by 4.33 ± 0.33 lg, which indicates that β-propiolactone is an effective inactivating agent. Five minutes of exposure to UV radiation reduces the RAV-1 strain viral load by 4.22 ± 0.31 lg and RAV-2 strain viral load by 4.44 ± 0.48 lg.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>гриппозные вакцины</kwd><kwd>инактивация</kwd><kwd>вирус лейкоза птиц</kwd><kwd>RAV-1</kwd><kwd>RAV-2</kwd><kwd>пропиолактон</kwd><kwd>УФ-излучение</kwd></kwd-group><kwd-group xml:lang="en"><kwd>influenza vaccines</kwd><kwd>inactivation</kwd><kwd>avian leucosis virus</kwd><kwd>RAV-1</kwd><kwd>RAV-2</kwd><kwd>propiolactone</kwd><kwd>UV radiation</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">EMA/CHMP/BWP/310834/2012 Rev.1 Committee for Medicinal Products for Human use (CHMP) Guideline on Influenza vaccines — Quality module, 2017.</mixed-citation><mixed-citation xml:lang="en">EMA/CHMP/BWP/310834/2012 Rev.1 Committee for Medicinal Products for Human use (CHMP) Guideline on Influenza vaccines — Quality module, 2017.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Рекомендации по производству и контролю вакцины против гриппа инактивированной, Приложение 3 серии технических докладов ВОЗ № 927, 2005.</mixed-citation><mixed-citation xml:lang="en">Rekomendacii po proizvodstvu i kontrolyu vakciny protiv grippa inaktivirovannoj, Prilozhenie 3 serii texnicheskix dokladov VOZ # 927, 2005. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Sabbaghi A, Miri SM, Keshavarz M, Zargar M, Ghaemi A. Inactivation methods for whole influenza vaccine production. Rev Med Virol. 2019; 29 (6): e2074.</mixed-citation><mixed-citation xml:lang="en">Sabbaghi A, Miri SM, Keshavarz M, Zargar M, Ghaemi A. Inactivation methods for whole influenza vaccine production. Rev Med Virol. 2019; 29 (6): e2074.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Савина Н. Н., Екимов А. А., Трухин В. П., Евтушенко А. Э., Жиренкина Е. Н., Синегубова Е. О. и др. Оценка методов инактивирования аденовируса птиц при производстве гриппозных вакцин. Медицина экстремальных ситуаций. 2021; (3): 84–9.</mixed-citation><mixed-citation xml:lang="en">Savina NN, Ekimov AA, Trukhin VP, Evtushenko AE, Zhirenkina EN, Sinegubova EO. Evaluation of avian adenovirus inactivation methods used in the production of influenza vaccines. Extreme Medecine. 2021; (3): 84–9.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Плотников В. А., Гребенникова Т. В., Дудникова Е. К., Шульпин М. И., Лазарева С. П., Никонова З. Б., и др. О распространении вируса лейкоза птиц в птицеводческих хозяйствах на территории России. Сельскохозяйственная биология. 2013; 6: 36–42.</mixed-citation><mixed-citation xml:lang="en">Plotnikov VA, Grebennikova TV, Dudnikova EK, Shulpin MI, Lazareva SP, Nikonova ZB, i dr. O rasprostranenii virusa lejkoza ptic v pticevodcheskix xozyajstvax na territorii Rossii. Sel'skoxozyajstvennaya biologiya. 2013; 6: 36–42. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Bister K, Varmus HE, Stavnezer E, Hunters E, Vogt PK. Biological and biochemical studies on the inactivation of avian oncoviruses by ultraviolet irradiation. Virology. 1977; 77 (2): 689–704.</mixed-citation><mixed-citation xml:lang="en">Bister K, Varmus HE, Stavnezer E, Hunters E, Vogt PK. Biological and biochemical studies on the inactivation of avian oncoviruses by ultraviolet irradiation. Virology. 1977; 77 (2): 689–704.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Herrera-Rodriguez J, Signorazzi A, Holtrop M, de Vries-Idema J, Huckriede A. Inactivated or damaged? Comparing the effect of inactivation methods on influenza virions to optimize vaccine production. Vaccine. 2019; 37 (12): 1630–7.</mixed-citation><mixed-citation xml:lang="en">Herrera-Rodriguez J, Signorazzi A, Holtrop M, de Vries-Idema J, Huckriede A. Inactivated or damaged? Comparing the effect of inactivation methods on influenza virions to optimize vaccine production. Vaccine. 2019; 37 (12): 1630–7.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Kap M, Arron GI, Loibner M, Hausleitner A, Siaulyte G, Zatloukal K, Riegman P. Inactivation of Influenza A virus, Adenovirus, and Cytomegalovirus with PAXgene Tissue Fixative and Formalin. Biopreservation and Biobanking. 2013; 11 (4): 229–34.</mixed-citation><mixed-citation xml:lang="en">Kap M, Arron GI, Loibner M, Hausleitner A, Siaulyte G, Zatloukal K, Riegman P. Inactivation of Influenza A virus, Adenovirus, and Cytomegalovirus with PAXgene Tissue Fixative and Formalin. Biopreservation and Biobanking. 2013; 11 (4): 229–34.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Shuo Lei, Xun Gao, Yang Sun, Xiangyong Yu, Longshan Zhao, Gas chromatography-mass spectrometry method for determination of β-propiolactone in human inactivated rabies vaccine and its hydrolysis analysis, Journal of Pharmaceutical Analysis. 2018; 8 (6): 373–7.</mixed-citation><mixed-citation xml:lang="en">Shuo Lei, Xun Gao, Yang Sun, Xiangyong Yu, Longshan Zhao, Gas chromatography-mass spectrometry method for determination of β-propiolactone in human inactivated rabies vaccine and its hydrolysis analysis, Journal of Pharmaceutical Analysis. 2018; 8 (6): 373–7.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Руководство по исследованию валидации вирусной очистки: проектирование, вклад и интерпретация исследований, использующих инактивацию и удаление вирусов, EMA CPMP/BWP/268/95, 1996.</mixed-citation><mixed-citation xml:lang="en">Rukovodstvo po issledovaniyu validacii virusnoj ochistki: proektirovanie, vklad i interpretaciya issledovanij, ispol'zuyushhix inaktivaciyu i udalenie virusov, EMA CPMP/BWP/268/95, 1996. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Фрешни Р. Я. Культура животных клеток: практическое руководство. Пер. 5-го англ. изд. М.: БИНОМ. Лаборатория знаний, 2018; 691 с.</mixed-citation><mixed-citation xml:lang="en">Freshni RYa. Kul'tura zhivotnyx kletok: prakticheskoe rukovodstvo. Per. 5-go angl. izd. M.: BINOM. Laboratoriya znanij, 2018; 691 s. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Li Xue, Dong Xuan, Sun Xiaolong, Li Weihua, Zhao Peng, Cui Zhizhong, Wang Xin. Preparation and immunoprotection of subgroup B avian leukosis virus inactivated vaccine. Vaccine. 2013; 31 (46): 5479–85.</mixed-citation><mixed-citation xml:lang="en">Li Xue, Dong Xuan, Sun Xiaolong, Li Weihua, Zhao Peng, Cui Zhizhong, Wang Xin. Preparation and immunoprotection of subgroup B avian leukosis virus inactivated vaccine. Vaccine. 2013; 31 (46): 5479–85.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Zavala, Guillermo, Sunny Cheng. Detection and Characterization of Avian Leukosis Virus in Marek’s Disease Vaccines. Avian Diseases. 2006; 50 (2): 209–15.</mixed-citation><mixed-citation xml:lang="en">Zavala, Guillermo, Sunny Cheng. Detection and Characterization of Avian Leukosis Virus in Marek’s Disease Vaccines. Avian Diseases. 2006; 50 (2): 209–15.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Haussmann C, Hauschild F, Jobst B, Novartis AG. Improvements in preparation of influenza virus vaccine antigens. Патент США № US6986808P. 18.03.2008.</mixed-citation><mixed-citation xml:lang="en">Haussmann C, Hauschild F, Jobst B, Novartis AG. Improvements in preparation of influenza virus vaccine antigens. Патент США № US6986808P. 18.03.2008.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Burt DS, Jones DH, Lowell GH, White GL, Torossian K, Fries LF. ID Biomedical Corp of Quebec. Proteosome influenza vaccine. Патент США № US18247600P. 15.02.2000.</mixed-citation><mixed-citation xml:lang="en">Burt DS, Jones DH, Lowell GH, White GL, Torossian K, Fries LF. ID Biomedical Corp of Quebec. Proteosome influenza vaccine. Патент США № US18247600P. 15.02.2000.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Трухин В. П., Евтушенко А. Э., Красильников И. В., Савина Н. Н., Быков Д. Г., Уйба С. В., Васильев А. Н., Рыськова Е. В., Начарова Е. П., Аракелов С. А., авторы. Федеральное государственное унитарное предприятие «Санкт-Петербургский научно-исследовательский институт вакцин и сывороток и предприятие по производству бактерийных препаратов» Федерального медико-биологического агентства (ФГУП СПбНИИВС ФМБА России). Способ получения антигена или антигенов для производства противогриппозной вакцины и вакцина на его основе. Патент РФ № RU2019118695A. 14.06.2019.</mixed-citation><mixed-citation xml:lang="en">Truhin VP, Evtushenko AJe, Krasilnikov IV, Savina NN, Bykov DG, Ujba SV, Vasilev AN, Ryskova EV, Nacharova EP, Arakelov SA, avtory. Federal'noe gosudarstvennoe unitarnoe predpriyatie «Sankt-Peterburgskij nauchno-issledovatel'skij institut vakcin i syvorotok i predpriyatie po proizvodstvu bakterijnyx preparatov» Federal'nogo mediko-biologicheskogo agentstva (FGUP SPbNIIVS FMBA Rossii). Sposob polucheniya antigena ili antigenov dlya proizvodstva protivogrippoznoj vakciny i vakcina na ego osnove. Patent RF # RU2019118695A. 14.06.2019. Russian.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
